Integrative analysis of immune microenvironment-related CeRNA regulatory axis in gastric cancer

Chen, Jie; Chen, Jing Gui; Sun, Bo; Wu, Jinhua; Du, Changqing

doi:10.3934/mbe.2020219

Cited by 11 publications

(7 citation statements)

References 45 publications

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“…The results showed that both high expression FTO and ALKBH5 showed a positive correlation with the number of T cells CD4 memory resting and a negative correlation with the number of neutrophils. Recent studies have reported that resting memory CD4 T cells are closely related with the pathogenesis of various malignant tumors, including GC, and pointed out that they might be affected by the key genes (28). Numerous studies have demonstrated that neutrophils play a key role in various tumors, including the promotion of lymph node metastasis in early GC, and high levels of tumor-associated neutrophils also promote GC progression and are associated with poor clinical prognosis (29).…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Value of m6A “Eraser” Related Gene Signature in Gastric Cancer

Zhou

Zheng

et al. 2021

Front. Oncol.

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BackgroundN6-methyladenosine (m6A) RNA modification plays a critical role in gastric cancer (GC). However, the relationship between the m6A “eraser”, FTO, and ALKBH5, and the prognosis of GC still remains unclear. This study aimed to evaluate the effect of FTO and ALKBH5 on the prognosis of patients and their potential roles in GC.Materials and MethodsA total of 738 GC samples with clinical information obtained from two independent datasets were included and divided into training set and testing set. Differential expression analysis of the m6A “eraser” related genes was performed. The LASSO Cox regression model was constructed to analyze the m6A “eraser” related risk genes. The univariate and multivariate Cox regression model were employed to identify the independent prognostic factors. Kaplan-Meier method was used for survival analysis. A nomogram model was then carried out to predict the prognosis of GC patients. Additionally, GO and KEGG analyses were conducted to identify the potential role of the m6A “eraser” related genes in GC. The relative proportion of 22 different genotypes in immune infiltrating cells was calculated by CIBERSORT algorithm.ResultsIn total, nine m6A “eraser” related risk genes and risk scores were obtained and calculated. Patients in high-risk group demonstrated significantly worse prognosis than those in low-risk group. Age, stage, and risk score were considered as independent prognostic factors. The nomogram model constructed accurately predicted the 3-year and 5-year overall survival (OS) of patients. Furthermore, m6A “eraser” might play a functional role in GC. The expression of m6A “eraser” leads to changes in tumor immune microenvironment.ConclusionsFTO and ALKBH5 showed association with the prognosis of GC. The m6A “eraser” related genes, which is considered as a reliable prognostic and predictive tool, assists in predicting the OS in GC patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Value of m6A “Eraser” Related Gene Signature in Gastric Cancer

Zhou

Zheng

et al. 2021

Front. Oncol.

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“…The KEGG pathway analysis showed that NOTCH genes-strongly correlated genes were most significantly enriched in the PI3K/Akt pathway in STAD. The PI3K/Akt pathway has been chiefly implicated in tumor metastasis and chemotherapy resistance, and PIK3CA is a well-recognized oncogene whose mutations are associated with gastric cancer [ 61 , 62 ]. Furthermore, a synergistic effect of NOTCH1 and PI3K/Akt inhibition on restricting gastric cancer has been reported [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Bioinformatic Analysis of NOTCH Pathway Involvement in Stomach Adenocarcinoma

Xue

Dou

et al. 2021

Disease Markers

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Background. Activation of NOTCH signaling pathways, which are key regulators of multiple cellular functions, has been frequently implicated in cancer pathogenesis, and NOTCH inhibitors have received much recent focus in the context of cancer therapeutics. However, the role and possible involvement of NOTCH pathways in stomach adenocarcinoma (STAD) are unclear. Here, putative regulatory mechanisms and functions of NOTCH pathways in STAD were investigated. Methods. Publicly available data from the TCGA-STAD database were utilized to explore the involvement of canonical NOTCH pathways in STAD by analyzing RNA expression levels of NOTCH receptors, ligands, and downstream genes. Statistical analysis of the data pertaining to cancer and noncancerous samples was performed using R software packages and public databases/webservers. Results. Significant differential gene expression between control and STAD samples was noted for all NOTCH receptors (NOTCH1, 2, 3, and 4), the delta-like NOTCH ligands (DLL-3 and 4), and typical downstream genes (HES1 and HEY1). Four genes (NOTCH1, NOTCH2, NOTCH3, and HEY1) presented prognostic values for the STAD outcome in terms of overall survival. Functional enrichment analysis indicated that NOTCH family genes-strongly correlated genes were mainly enriched in several KEGG signaling pathways such as the PI3K-Akt signaling pathway, human papillomavirus infection, focal adhesion, Rap1 signaling pathway, and ECM-receptor interaction. Gene set enrichment analysis (GSEA) results showed that NOTCH family genes-significantly correlated genes were mainly enriched in four signaling pathways, ECM (extracellular matrix), tumor angiogenesis, inflammatory response, and immune regulation. Conclusions. NOTCH family genes may play an essential role in the progression of STAD by modulating immune cells and mediating ECM synthesis, angiogenesis, focal adhesion, and PI3K-Akt signaling. Multiple NOTCH family genes are valuable candidate biomarkers or therapeutic targets for the management of STAD.

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“…In contrast to the previous research on IRLs in GC [ 42 – 44 ], the current study comprehensively evaluated the immune-related ceRNA network for the first time, established the risk model, and preliminarily validated the related lncRNAs. Additionally, the finding also suggested that RP11-617F23.1 may be used as a prognostic predictor for GC.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Prognostic Immune-Related LncRNA Risk Model for Gastric Cancer

Ding

Sun

Tan

et al. 2022

Journal of Oncology

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Gastric cancer (GC) is one of the most common malignancies, and novel prognostic biomarkers for it are urgently required. This study is aimed at screening a group of immune-related lncRNAs (IRLs) in predicting the prognosis of GC patients. Genetic and clinical information from the 360 GC patients was included in this study. Eight IRLs in lncRNA-miRNA-mRNA network were screened out according to differential expression analysis. A novel risk score model with three IRLs (MIR4435-1HG, UCA1, and RP11-617F23.1) were identified, and patients were assigned to a high-risk group and a low-risk group. Patients in the low-risk group had a better prognosis. In addition, two nomograms were developed to predict the prognosis of GC. We evaluated the correlation between IRLs and the immune infiltration level of GC using TIMER. Furthermore, we verified that RP11-617F23.1 was significantly upregulated in human GC tissues compared with their adjacent tissues. And, patients with high RP11-617F23.1 expression in tumor tissues had poorer survival. In conclusion, we established a novel risk model based on IRLs for predicting the prognosis of GC. Meanwhile, a novel IRL, RP11-617F23.1, could serve as a predictor of prognosis for patients with GC.

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Integrative analysis of immune microenvironment-related CeRNA regulatory axis in gastric cancer

Cited by 11 publications

References 45 publications

Prognostic and Predictive Value of m6A “Eraser” Related Gene Signature in Gastric Cancer

Prognostic and Predictive Value of m6A “Eraser” Related Gene Signature in Gastric Cancer

A Comprehensive Bioinformatic Analysis of NOTCH Pathway Involvement in Stomach Adenocarcinoma

Construction of a Prognostic Immune-Related LncRNA Risk Model for Gastric Cancer

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